scholarly journals Neurons in the Nucleus Tractus Solitarius are Selective to the Orientation of Gastric Electrical Stimulation

2021 ◽  
Author(s):  
Jiayue Cao ◽  
Xiaokai Wang ◽  
Terry L Powley ◽  
Zhongming Liu
Keyword(s):  
Smooth Muscle ◽  
Electrical Stimulation ◽  
Nucleus Tractus Solitarius ◽  
Functional Gastrointestinal Disorders ◽  
Smooth Muscles ◽  
Gastric Electrical Stimulation ◽  
Vagal Afferents ◽  
Stimulus Orientation ◽  
Afferent Neurons ◽  
Vagal Afferent

Gastric electrical stimulation (GES) is a bioelectric intervention for gastroparesis, obesity, and other functional gastrointestinal disorders. In a potential mechanism of action, GES activates the nerve endings of vagal afferent neurons and induces the vago-vagal reflex through the nucleus tractus solitarius (NTS) in the brainstem. However, it is unclear where and how to stimulate in order to optimize the vagal afferent responses. To address this question with electrophysiology in rats, we applied mild electrical currents to two serosal targets on the distal forestomach with dense distributions of vagal intramuscular arrays that innervated the circular and longitudinal smooth muscle layers. During stimulation, we recorded single and multi-unit responses in NTS and evaluated how the recorded responses depended on the stimulus orientation and amplitude. We found that NTS responses were highly selective to the stimulus orientation for a range of stimulus amplitudes. The strongest responses were observed when the applied current flowed in the same direction as the intramuscular arrays in parallel with the underlying smooth muscle fibers. Our results suggest that gastric neurons in NTS may encode the orientation-specific activity of gastric smooth muscles relayed by vagal afferent neurons. This finding suggests that the orientation of GES is critical to effective engagement of vagal afferents and should be considered in light of the structural phenotypes of vagal terminals in the stomach.

Peripheral oxytocin activates vagal afferent neurons to suppress feeding in normal and leptin-resistant mice: a route for ameliorating hyperphagia and obesity

2015 ◽  
Vol 308 (5) ◽  
pp. R360-R369 ◽  
Author(s):  
Yusaku Iwasaki ◽  
Yuko Maejima ◽  
Shigetomo Suyama ◽  
Masashi Yoshida ◽  
Takeshi Arai ◽  
...  
Keyword(s):  
Food Intake ◽  
Nucleus Tractus Solitarius ◽  
Body Weight Gain ◽  
Vagal Afferents ◽  
Afferent Neuron ◽  
Afferent Neurons ◽  
Vagal Afferent ◽  
Fos Expression ◽  
Novel Target ◽  
Anorexigenic Effect

Oxytocin (Oxt), a neuropeptide produced in the hypothalamus, is implicated in regulation of feeding. Recent studies have shown that peripheral administration of Oxt suppresses feeding and, when infused subchronically, ameliorates hyperphagic obesity. However, the route through which peripheral Oxt informs the brain is obscure. This study aimed to explore whether vagal afferents mediate the sensing and anorexigenic effect of peripherally injected Oxt in mice. Intraperitoneal Oxt injection suppressed food intake and increased c-Fos expression in nucleus tractus solitarius to which vagal afferents project. The Oxt-induced feeding suppression and c-Fos expression in nucleus tractus solitarius were blunted in mice whose vagal afferent nerves were blocked by subdiaphragmatic vagotomy or capsaicin treatment. Oxt induced membrane depolarization and increases in cytosolic Ca2+ concentration ([Ca2+]i) in single vagal afferent neurons. The Oxt-induced [Ca2+]i increases were markedly suppressed by Oxt receptor antagonist. These Oxt-responsive neurons also responded to cholecystokinin-8 and contained cocaine- and amphetamine-regulated transcript. In obese diabetic db/db mice, leptin failed to increase, but Oxt increased [Ca2+]i in vagal afferent neurons, and single or subchronic infusion of Oxt decreased food intake and body weight gain. These results demonstrate that peripheral Oxt injection suppresses food intake by activating vagal afferent neurons and thereby ameliorates obesity in leptin-resistant db/db mice. The peripheral Oxt-regulated vagal afferent neuron provides a novel target for treating hyperphagia and obesity.

Responses of medullary raphe neurons to electrical and chemical activation of vagal afferent nerve fibers

1993 ◽  
Vol 70 (5) ◽  
pp. 1950-1961 ◽  
Author(s):  
A. R. Evans ◽  
R. W. Blair
Keyword(s):  
Electrical Stimulation ◽  
Chemical Activation ◽  
Vagal Afferents ◽  
Frequency Dependent ◽  
Afferent Fibers ◽  
Vagal Afferent ◽  
Mixed Responses ◽  
Excitatory Responses ◽  
Dose Dependent ◽  
Stimulation Of

1. Various intensities, frequencies, and pulse widths of electrical stimulation of vagal afferent fibers were used to assess the responses of 87 medullary raphe neurons to vagal afferent fiber input in pentobarbital sodium-anesthetized, barodenervated paralyzed cats. Thirty-seven neurons were antidromically activated from the T2-T3 segments of the thoracic spinal cord, and 40 neurons could not be antidromically activated. Neurons were located in the nucleus raphe magnus (79%) and the nucleus raphe obscurus (15%). The remaining 6% of the neurons were not found; however, their locations were comparable in depth and position on the midline with other neurons in the same animals whose locations were identified. 2. The responses of 60 neurons to electrical stimulation of vagal afferent fibers were classified as excitatory (38%), inhibitory (24%), or mixed, (7%). The mixed responses were characterized by excitation at one frequency or intensity and inhibition at another frequency or intensity. The remaining 27 neurons did not clearly respond. 3. The excitatory responses to electrical stimulation of the cervical vagus nerve were intensity and frequency dependent. Inhibitory responses were frequency dependent at lower frequencies of stimulation and both frequency and intensity dependent at higher frequencies. The mixed responses were frequency dependent. Overall, longer pulse widths produced significantly greater responses than shorter pulse widths. 4. Thirty-three neurons were tested for responses to chemical stimulation of vagal afferents with intra-atrial injections of three doses of veratridine. Twenty-one percent were excited, 55% were inhibited, and 6% had mixed responses. For the mixed responses, excitation occurred at one dose and inhibition at another. The remaining 18% of the neurons were unresponsive to veratridine. The excitatory responses were dose dependent, but the inhibitory responses were not. Three doses of phenybiguanide (PBG) were also used to chemically activate vagal afferents in 27 neurons. Eleven percent were excited, 44% were inhibited, and 4% had mixed responses. The remaining 41% were unresponsive to PBG. The excitatory and inhibitory responses were dose dependent. 5. When comparing responses in projection and nonprojection neurons, inhibition was seen significantly more often in projection neurons and excitation in nonprojection neurons. Sixty-three percent of the neurons inhibited by electrical stimulation were raphespinal neurons, and 78% of the neurons excited by vagal stimulation were nonprojection neurons. Similar observations were made with the responses to chemical activation of the vagus. 6. Neurons with lower spontaneous discharge rates were more often excited by vagal stimulation and neurons with higher rates were more often inhibited.(ABSTRACT TRUNCATED AT 400 WORDS)

Leptin and CCK modulate complementary background conductances to depolarize cultured nodose neurons

2006 ◽  
Vol 290 (2) ◽  
pp. C427-C432 ◽  
Author(s):  
J. H. Peters ◽  
R. C. Ritter ◽  
S. M. Simasko
Keyword(s):  
Food Intake ◽  
Outward Current ◽  
Vagal Afferents ◽  
Afferent Neurons ◽  
Inward Current ◽  
Adult Rat ◽  
Nodose Ganglia ◽  
Sodium Dependent ◽  
Ionic Mechanisms ◽  
Vagal Afferent

We have previously reported that intraceliac infusion of leptin induces a reduction of meal size that depends on intact vagal afferents. This effect of leptin is enhanced in the presence of cholecystokinin (CCK). The mechanisms by which leptin and CCK activate vagal afferent neurons are not known. In the present study, we have begun to address this question by using patch-clamp electrophysiological techniques to examine the mechanisms by which leptin and CCK activate cultured vagal afferents from adult rat nodose ganglia. We found that leptin depolarized 41 (60%) of 68 neurons. The magnitude of membrane depolarization was dependent on leptin concentration and occurred in both capsaicin-sensitive and capsaicin-insensitive neurons. We also found that a majority (16 of 22; 73%) of nodose neurons activated by leptin were also sensitive to CCK. CCK-induced depolarization was primarily associated with the increase of an inward current (11 of 12), whereas leptin induced multiple changes in background conductances through a decrease in an outward current (7 of 13), an increase in an inward current (3 of 13), or both (3 of 13). However, further isolation of background currents by recording in solutions that contained only sodium or only potassium revealed that both leptin and CCK were capable of increasing a sodium-dependent conductance or inhibiting a potassium-dependent conductance. Our results support the hypothesis that vagal afferents are a point of convergence and integration of leptin and CCK signaling for control of food intake and suggest multiple ionic mechanisms by which leptin and CCK activate vagal afferent neurons.

The abdominal visceral innervation and the emetic reflex: pathways, pharmacology, and plasticity

1990 ◽  
Vol 68 (2) ◽  
pp. 325-345 ◽  
Author(s):  
P. L. R. Andrews ◽  
C. J. Davis ◽  
S. Bingham ◽  
H. I. M. Davidson ◽  
J. Hawthorn ◽  
...  
Keyword(s):  
Nucleus Tractus Solitarius ◽  
Area Postrema ◽  
Cytotoxic Drugs ◽  
Vagal Afferents ◽  
Laboratory Animals ◽  
Receptor Antagonists ◽  
Wide Range ◽  
Vagal Afferent ◽  
Afferent Terminals ◽  
Visceral Innervation

In recent years the role of the area postrema in the emetic reflex has been predominant and the involvement of the abdominal visceral innervation has tended to be overlooked. This paper attempts to redress the balance reflex by reviewing aspects of the existing literature and complementing this with original studies from the ferret. In view of the widespread use of the ferret in studies of emesis and particularly in the characterization of the antiemetic actions of 5-HT3 receptor antagonist, the opportunity is taken to assess the suitability of this species for studies of emesis. It is concluded that the ferret is sensitive to a wide range of emetic stimuli including intragastric irritants, opiate and dopamine receptor agonists, many cytotoxic drugs, and radiation. For several stimuli it is more sensitive than other species and for radiation on the basis of its ED100 it appears to be the most sensitive of the laboratory animals studied. Using electrical stimulation of the central end of the dorsal vagal trunk in the abdomen in conscious and anaesthetized animals, the vagal afferents were shown to be capable of eliciting emesis. Using lesioning studies an involvement of the vagus in the emetic response to a number of cytotoxic drugs (e.g., cisplatinum, cyclophosphamide, mustine) and radiation was demonstrated, although the magnitude of the effect varied with the different stimuli. An attempt is made to reconcile these observations with previous studies of area postrema ablation. The problems of interpreting the effects of nerve lesions are critically discussed in light of preliminary evidence presented here that there may be a degree of plasticity in the emetic pathway following such lesions. The range of antiemetic effects of 5-HT3 receptor antagonists is reviewed and an attempt is made to identify the site(s) at which these agents act. Results are presented that suggest a link between the vagus and 5-HT3 receptor antagonism. These studies are discussed together with others and lead us to propose that (in the ferret) 5-HT3 receptor antagonists have their main antiemetic effect by acting on vagal afferent terminals in the wall of the upper gut with an additional minor site either in the nucleus tractus solitarius or presynaptically on the vagal afferent terminals in the medulla where binding sites for 5-HT3 receptor ligands have recently been demonstrated in this species.Key words: emesis, visceral nerves, vagus nerve, ferret, plasticity, serotonin antagonists.

scholarly journals Expression of transient receptor potential channels and two-pore potassium channels in subtypes of vagal afferent neurons in rat

2010 ◽  
Vol 298 (2) ◽  
pp. G212-G221 ◽  
Author(s):  
Huan Zhao ◽  
Leslie K. Sprunger ◽  
Steven M. Simasko
Keyword(s):  
Single Cell ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Channels ◽  
Vagal Afferents ◽  
Afferent Neurons ◽  
Single Cell Pcr ◽  
Nodose Ganglia ◽  
Vagal Afferent ◽  
Transient Receptor

Vagal afferent neurons relay important information regarding the control of the gastrointestinal system. However, the ionic mechanisms that underlie vagal activation induced by sensory inputs are not completely understood. We postulate that transient receptor potential (TRP) channels and/or two-pore potassium (K2p) channels are targets for activating vagal afferents. In this study we explored the distribution of these channels in vagal afferents by quantitative PCR after a capsaicin treatment to eliminate capsaicin-sensitive neurons, and by single-cell PCR measurements in vagal afferent neurons cultured after retrograde labeling from the stomach or duodenum. We found that TRPC1/3/5/6, TRPV1-4, TRPM8, TRPA1, TWIK2, TRAAK, TREK1, and TASK1/2 were all present in rat nodose ganglia. Both lesion results and single-cell PCR results suggested that TRPA1 and TRPC1 were preferentially expressed in neurons that were either capsaicin sensitive or TRPV1 positive. Expression of TRPM8 varied dynamically after various manipulations, which perhaps explains the disparate results obtained by different investigators. Last, we also examined ion channel distribution with the A-type CCK receptor (CCK-RA) and found there was a significant preference for neurons that express TRAAK to also express CCK-RA, especially in gut-innervating neurons. These findings, combined with findings from prior studies, demonstrated that background conductances such as TRPC1, TRPA1, and TRAAK are indeed differentially distributed in the nodose ganglia, and not only do they segregate with specific markers, but the degree of overlap is also dependent on the innervation target.

scholarly journals Cooperative Activation of Cultured Vagal Afferent Neurons by Leptin and Cholecystokinin

Endocrinology ◽  
2004 ◽  
Vol 145 (8) ◽  
pp. 3652-3657 ◽  
Author(s):  
J. H. Peters ◽  
A. B. Karpiel ◽  
R. C. Ritter ◽  
S. M. Simasko
Keyword(s):  
Primary Cultures ◽  
Cytosolic Calcium ◽  
Extracellular Calcium ◽  
Vagal Afferents ◽  
Afferent Neurons ◽  
Adult Rat ◽  
Nodose Ganglia ◽  
Vagal Afferent ◽  
Acute Changes ◽  
And Control

Abstract To test the hypothesis that leptin can directly activate vagal afferent neurons, we used fluorescence imaging to detect acute changes in cytosolic calcium after leptin application to primary cultures of vagal afferent neurons dissociated from adult rat nodose ganglia. We found that approximately 40% of vagal afferent neurons exposed to leptin (40 ng/ml) responded with rapid and reversible increases in cytosolic calcium. These responses were dependent upon extracellular calcium. As previously reported, about 35% of vagal afferents increase cytosolic calcium in response to the gut-peptide cholecystokinin (CCK). A majority (74%) of neurons that responded to CCK also exhibited increases in cytosolic calcium in response to leptin. In addition, synergistic increases in cytosolic calcium were observed when leptin and CCK were applied in combination. These results demonstrate that leptin acts directly on vagal afferent neurons to trigger acute influxes of extracellular calcium. Our results also suggest cooperation between leptin and CCK in the activation of some vagal afferent neurons. Acute activation of vagal afferents by leptin alone and in combination with CCK may contribute to modulation of visceral reflexes and control of food intake.

Enhancement of antral contractions and vagal afferent signaling with synchronized electrical stimulation

2003 ◽  
Vol 285 (3) ◽  
pp. G577-G585 ◽  
Author(s):  
Shachar Peles ◽  
Jaime Petersen ◽  
Ricardo Aviv ◽  
Shai Policker ◽  
Ossama Abu-Hatoum ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Vagal Afferents ◽  
Mechanical Stimuli ◽  
The Central Nervous System ◽  
Rhythmic Firing ◽  
Vagal Afferent ◽  
Electrically Enhanced ◽  
Smooth Muscle Contractions ◽  
Afferent Signaling ◽  
Antral Distension

Gastric filling activates vagal afferents involved in peripheral signaling to the central nervous system (CNS) for food intake. It is not known whether these afferents linearly encode increasing contractions of the antrum during antral distension (AD). The aim of this study was to investigate effects of AD and electrically enhanced antral contractions on responses of vagal afferents innervating the antrum. Single-fiber recordings were made from the vagal afferents in anesthetized male Long-Evans rats. Antral contractions were measured with a solid-state probe placed in the antrum. A nonexcitatory electrical stimulation (NES) inducing no smooth muscle contractions was applied during the ascending phase of antral contractions to enhance subsequent antral contractions. Fifty-six fibers identified during AD (1 ml for 30 s) were studied through different types of mechanical stimuli. Under normal conditions, one group of fibers exhibited rhythmic firing in phase with antral contractions. Another group of fibers had nonrhythmic spontaneous firing. Responses of 15 fibers were tested with NES during multiple-step distension (MSD). NES produced a mean increase in antral contraction amplitude (177.1 ± 35.3%) and vagal afferent firing (21.6 ± 2.6%). Results show that both passive distension and enhanced antral contractions activate distension-sensitive vagal afferents. Responses of these fibers increase linearly to enhanced antral contraction induced by NES or MSD up to a distending volume of 0.6 ml. However, responses reached a plateau at a distending volume >0.8 ml. We concluded that enhanced contraction of the antrum can activate vagal afferents signaling to the CNS.

scholarly journals Loss of neurotrophin-3 from smooth muscle disrupts vagal gastrointestinal afferent signaling and satiation

2013 ◽  
Vol 305 (11) ◽  
pp. R1307-R1322 ◽  
Author(s):  
Edward A. Fox ◽  
Jessica E. Biddinger ◽  
Zachary C. Baquet ◽  
Kevin R. Jones ◽  
Jennifer McAdams
Keyword(s):  
Smooth Muscle ◽  
Area Postrema ◽  
Microstructural Analysis ◽  
Meal Size ◽  
Vagal Afferents ◽  
Eating Rate ◽  
Daily Food ◽  
Neurotrophin 3 ◽  
Vagal Afferent ◽  
Afferent Signaling

A large proportion of vagal afferents are dependent on neurotrophin-3 (NT-3) for survival. NT-3 is expressed in developing gastrointestinal (GI) smooth muscle, a tissue densely innervated by vagal mechanoreceptors, and thus could regulate their survival. We genetically ablated NT-3 from developing GI smooth muscle and examined the pattern of loss of NT-3 expression in the GI tract and whether this loss altered vagal afferent signaling or feeding behavior. Meal-induced c-Fos activation was reduced in the solitary tract nucleus and area postrema in mice with a smooth muscle-specific NT-3 knockout ( SM-NT-3 KO) compared with controls, suggesting a decrease in vagal afferent signaling. Daily food intake and body weight of SM-NT-3 KO mice and controls were similar. Meal pattern analysis revealed that mutants, however, had increases in average and total daily meal duration compared with controls. Mutants maintained normal meal size by decreasing eating rate compared with controls. Although microstructural analysis did not reveal a decrease in the rate of decay of eating in SM-NT-3 KO mice, they ate continuously during the 30-min meal, whereas controls terminated feeding after 22 min. This led to a 74% increase in first daily meal size of SM-NT-3 KO mice compared with controls. The increases in meal duration and first meal size of SM-NT-3 KO mice are consistent with reduced satiation signaling by vagal afferents. This is the first demonstration of a role for GI NT-3 in short-term controls of feeding, most likely involving effects on development of vagal GI afferents that regulate satiation.

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